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Chest. 2017 May;151(5):971-981. doi: 10.1016/j.chest.2016.10.061. Epub 2016 Nov 24.

Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial.

Author information

1
Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL; Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL; Department of Pediatrics, University of Miami Leonard M. Miller School of Medicine, Miami, FL. Electronic address: mglassbe@med.miami.edu.
2
Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
3
Department of Medicine, Florida International University Herbert Wertheim College of Medicine, Miami, FL.
4
Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL.
5
Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL; University of Miami Interdisciplinary Stem Cell Institute, Miami, FL.
6
Department of Cardiology, University of Louisville, Louisville, KY.
7
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
8
Bristol-Myers Squibb, Lawrenceville, NJ.
9
Department of Medicine, University of Vermont College of Medicine, Burlington, VT.
10
The EMMES Corporation, Rockville, MD.

Abstract

BACKGROUND:

Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow-derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis.

METHODS:

Nine patients with mild to moderate IPF were sequentially assigned to 1 of 3 cohorts and dosed with a single IV infusion of 20, 100, or 200 × 106 human bone marrow-derived mesenchymal stem cells per infusion from young, unrelated, men. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary end point was the incidence (at week 4 postinfusion) of treatment-emergent serious adverse events, defined as the composite of death, nonfatal pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically significant laboratory test abnormalities. Safety was assessed until week 60 and additionally 28 days thereafter. Secondary efficacy end points were exploratory and measured disease progression.

RESULTS:

No treatment-emergent serious adverse events were reported. Two nontreatment-related deaths occurred because of progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks postinfusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted diffusing capacity of the lungs for carbon monoxide.

CONCLUSIONS:

Data from this trial support the safety of a single infusion of human mesenchymal stem cells in patients with mild-moderate IPF.

TRIAL REGISTRY:

ClinicalTrials.gov; No.: NCT02013700; URL: www.clinicaltrials.gov.

KEYWORDS:

bone marrow; idiopathic pulmonary fibrosis; mesenchymal stem cells; safety trial

PMID:
27890713
PMCID:
PMC6026255
DOI:
10.1016/j.chest.2016.10.061
[Indexed for MEDLINE]
Free PMC Article

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